Pressure Reactivity Index Research Articles

Optimal bispectral index level of sedation and cerebral oximetry in traumatic brain injury: a non-invasive individualized approach in critical care?

BackgroundImpaired cerebral autoregulation has been linked with worse outcomes, with literature suggesting that current therapy guidelines fail to significantly impact cerebrovascular reactivity. The cerebral oximetry index (COx_a) is a surrogate measure of cerebrovascular reactivity which can in theory be obtained non-invasively using regional brain tissue oxygen saturation and arterial blood pressure. The goal of this study was to assess the relationship between objectively measured depth of sedation through BIS and autoregulatory capacity measured through COx_a.MethodsIn a prospectively maintained observational study, we collected continuous regional brain tissue oxygen saturation, intracranial pressure, arterial blood pressure and BIS in traumatic brain injury patients. COx_a was obtained using the Pearson’s correlation between regional brain tissue oxygen saturation and arterial blood pressure and ranges from − 1 to 1 with higher values indicating impairment of cerebrovascular reactivity. Using BIS values and COx_a, a curve-fitting method was applied to determine the minimum value for the COx_a. The associated BIS value with the minimum COx_a is called BISopt. This BISopt was both visually and algorithmically determined, which were compared and assessed over the whole dataset.ResultsOf the 42 patients, we observed that most had a parabolic relationship between BIS and COx_a. This suggests a potential “optimal” depth of sedation where COx_a is the most intact. Furthermore, when comparing the BISopt algorithm with visual inspection of BISopt, we obtained similar results. Finally, BISopt % yield (determined algorithmically) appeared to be independent from any individual sedative or vasopressor agent, and there was agreement between BISopt found with COx_a and the pressure reactivity index (another surrogate for cerebrovascular reactivity).ConclusionsThis study suggests that COx_a is capable of detecting disruption in cerebrovascular reactivity which occurs with over-/under-sedation, utilizing a non-invasive measure of determination and assessment. This technique may carry implications for tailoring sedation in patients, focusing on individualized neuroprotection.

Proposal of a Management Algorithm to Predict the Need for Expansion Duraplasty in American Spinal Injury Association Impairment Scale Grades A-C Traumatic Cervical Spinal Cord Injury Patients.

Expansion duraplasty to reopen effaced subarachnoid space and improve spinal cord perfusion, autoregulation, and spinal pressure reactivity index (sPRX) has been advocated in patients with traumatic cervical spinal cord injury (tCSCI). We designed this study to identify candidates for expansion duraplasty, based on the absence of cerebrospinal fluid (CSF) interface around the spinal cord on magnetic resonance imaging (MRI), in the setting of otherwise adequate bony decompression. Over a 61-month period, 104 consecutive American Spinal Injury Association Impairment Scale (AIS) grades A-C patients with tCSCI had post-operative MRI to assess the adequacy of surgical decompression. Their mean age was 53.4 years, and 89% were male. Sixty-one patients had falls, 31 motor vehicle collisions, 11 sport injuries, and one an assault. The AIS grade was A in 56, B in 18, and C in 30 patients. Fifty-four patients had fracture dislocations; there was no evidence of skeletal injury in 50 patients. Mean intramedullary lesion length (IMLL) was 46.9 (standard deviation = 19.4) mm. Median time from injury to decompression was 17 h (interquartile range 15.2 h). After surgery, 94 patients had adequate decompression as judged by the presence of CSF anterior and posterior to the spinal cord, whereas 10 patients had effacement of the subarachnoid space at the injury epicenter. In two patients whose decompression was not definitive and post-operative MRI indicated inadequate decompression, expansion duraplasty was performed. Candidates for expansion duraplasty (i.e., those with inadequate decompression) were significantly younger (p < 0.0001), were AIS grade A (p < 0.0016), had either sport injuries (six patients) or motor vehicle collisions (three patients) (p < 0.0001), had fracture dislocation (p = 0.00016), and had longer IMLL (p = 0.0097). In regression models, patients with sport injuries and inadequate decompression were suitable candidates for expansion duraplasty (p = 0.03). Further, 9.6% of patients failed bony decompression alone and either did (2) or would have (8) benefited from expansion duraplasty.

Inducing oscillations in positive end-expiratory pressure improves assessment of cerebrovascular pressure reactivity in patients with traumatic brain injury.

The cerebral pressure reactivity index (PRx), through intracranial pressure (ICP) measurements, informs clinicians about the cerebral autoregulation (CA) status in adult-sedated patients with traumatic brain injury (TBI). Using PRx in clinical practice is currently limited by variability over shorter monitoring periods. We applied an innovative method to reduce the PRx variability by ventilator-induced slow (1/min) positive end-expiratory pressure (PEEP) oscillations. We hypothesized that, as seen in a previous animal model, the PRx variability would be reduced by inducing slow arterial blood pressure (ABP) and ICP oscillations without other clinically relevant physiological changes. Patients with TBI were ventilated with a static PEEP for 30 min (PRx period) followed by a 30-min period of slow [1/min (0.0167 Hz)] +5 cmH2O PEEP oscillations (induced (iPRx period). Ten patients with TBI were included. No clinical monitoring was discontinued and no additional interventions were required during the iPRx period. The PRx variability [measured as the standard deviation (SD) of PRx] decreased significantly during the iPRx period from 0.25 (0.22-0.30) to 0.14 (0.09-0.17) (P = 0.006). There was a power increase around the induced frequency (1/min) for both ABP and ICP (P = 0.002). In conclusion, 1/min PEEP-induced oscillations reduced the PRx variability in patients with TBI with ICP levels <22 mmHg. No other clinically relevant physiological changes were observed. Reduced PRx variability might improve CA-guided perfusion management by reducing the time to find "optimal" perfusion pressure targets. Larger studies with prolonged periods of PEEP-induced oscillations are required to take it to routine use.NEW & NOTEWORTHY Cerebral autoregulation assessment requires sufficient slow arterial blood pressure (ABP) waves. However, spontaneous ABP waves may be insufficient for reliable cerebral autoregulation estimations. Therefore, we applied a ventilator "sigh-function" to generate positive end-expiratory pressure oscillations that induce slow ABP waves. This method demonstrated a reduced variability of the pressure reactivity index, commonly used as continuous cerebral autoregulation measure in a traumatic brain injury population.

It's a Bit Crowded in Here: Examining Pressure Reactivity in Craniocerebral Disproportion

Pressure reactivity index (PRx) is a measure used to gain insights into cerebrovascular reactivity. It is generally used in acute settings such as traumatic brain injury and subarachnoid hemorrhage, however there is limited data on its utility in cases of slow compensatory changes in intracranial pressure such as craniocerebral disproportion. Here we illustrate a case of how PRx can provide valuable information in such settings.

Monitoring of cerebrovascular pressure reactivity in children may predict neurologic outcome after hypoxic-ischemic brain injury

ObjectivesImpaired cerebral blood flow is a first-line reason of ischemic-hypoxic brain injury in children. The principal goal of intensive care management is to detect and prevent further cerebral blood flow deficits. This can be achieved by actively managing cerebral perfusion pressure (CPP) using input from cerebrovascular autoregulation (CAR). The main objective of the current study was to investigate CAR after cardiac arrest in children.MethodsNineteen consecutive children younger than 18 years after cardiopulmonary resuscitation, in whom intracranial pressure (ICP) was continuously measured, were included. Blood pressure and ICP were continuously monitored via ICM + software and actively managed using the pressure reactivity index (PRx) to achieve and maintain an optimal CPP. Outcome was scored using the extended Glasgow outcome scale (eGOS) at discharge and 6 months.ResultsEight children died in hospital. At 6 months, further 4 children had an unfavorable (eGOS1–4) and 7 a favorable (eGOS5–8) outcome. Over the entire monitoring period, we found an elevated ICP (24.5 vs 7.4 mmHg), a lower CPP (50.3 vs 66.2 mmHg) and a higher PRx (0.24 vs − 0.01), indicating impaired CAR, in patients with unfavorable outcome. The dose of impaired autoregulation was significantly higher in unfavorable outcome (54.6 vs 29.3%). Analyzing only the first 72 h after cardiac arrest, ICP ≥ 10 mmHg and PRx > 0.2 correlated to unfavorable outcome.ConclusionsSignificant doses of impaired CAR within 72 h after resuscitation are associated with unfavorable outcome. The inability to restore autoregulation despite active attempts to do so as well as an elevated ICP may serve as a bad prognostic sign indicating a severe initial hypoxic-ischemic brain injury.

Evaluation and Application of Ultra-Low-Resolution Pressure Reactivity Index in Moderate or Severe Traumatic Brain Injury.

The pressure reactivity index (PRx) has emerged as a surrogate method for the continuous bedside estimation of cerebral autoregulation and a predictor of unfavorable outcome after traumatic brain injury (TBI). However, calculation of PRx require continuous high-resolution monitoring currently limited to specialized intensive care units. The aim of this study was to evaluate a new index, the ultra-low-frequency PRx (UL-PRx) sampled at ∼0.0033 Hz at ∼5 minutes periods, and to investigate its association with outcome. Demographic data, admission Glasgow coma scale, in-hospital mortality and Glasgow outcome scale extended at 12 months were extracted from electronic records. The filtering and preparation of time series of intracranial pressure (ICP), mean arterial pressure and cerebral perfusion pressure (CPP), and calculation of the indices (UL-PRx, Δ-optimal CPP), were performed in MATLAB using an in-house algorithm. A total of 164 TBI patients were included in the study; in-hospital and 12-month mortality was 29.3% and 38.4%, respectively, and 64% of patients had poor neurological outcome at 12 months. On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month mortality. After adjusting for age, Glasgow coma scale, ICP and CPP, mean UL-PRx and UL-PRx thresholds of 0 and +0.25 remained associated with 12-month mortality. Similar findings were obtained for in-hospital mortality. For mean UL-PRx, the area under the receiver operating characteristic curves for in-hospital and 12-month mortality were 0.78 (95% confidence interval [CI]: 0.69-0.87; P <0.001) and 0.70 (95% CI: 0.61-0.79; P <0.001), respectively, and 0.65 (95% CI: 0.57-0.74; P =0.001) for 12-month neurological outcome. Our findings indicate that ultra-low-frequency sampling might provide sufficient resolution to derive information about the state of cerebrovascular autoregulation and prediction of 12-month outcome in TBI patients.

Abstract 272: Identifying Vascular Determinants Of Optimal Cerebral Perfusion Pressure In Traumatic Brain Injury Using A Continuous Measurement Algorithm.

Introduction: Individualized therapy targeting certain cerebral perfusion pressure (CPP) values in patients with traumatic brain injury may improve outcomes. One method to obtain “optimal” CPP (CPPopt) uses a measurement algorithm with continuous arterial blood pressure (ABP) and intracranial pressure (ICP) to estimate CPPopt where the pressure reactivity index is lowest. Yet, there is a knowledge gap regarding the cerebrovascular conditions that determine the algorithm’s success and validity. Here, we use a validated brain vasculature model to assess the algorithm’s performance at varying simulated vascular conditions. Methods: We used a convenience sample of 12 patient records with 4 hours of high-resolution ABP from the MIMIC III database. Each ABP set generated a synthetic ICP from our model. The algorithm then performed 38,815 CPPopt estimates across 12 patient records based on given input parameters. We examined “G”, an autoregulation parameter representing the sensitivity of ICP response to ABP change, and “Tau”, a time parameter representing the delay in ICP response to ABP change. We varied G and Tau independently and measured changes in frequency of algorithm success in finding CPPopt (CPPopt coverage), pressure reactivity index (PRx), and CPPopt itself. Results: 1.As G increases, CPPopt coverage, and mean minimum PRx decrease.2.As Tau increases, CPPopt coverage, and mean minimum PRx increase.3.CPPopt coverage had a median success rate of 27.111% and IQR of 29.118% across G and median success rate of 45.166% and IQR of 35.3362% across Tau for 38,815 algorithm estimates across the 12 patient records. Conclusion: The CPPopt algorithm may have a higher likelihood of finding CPPopt in pathological conditions where G is expected to be low and Tau to be large. The low and variable algorithm success rate poses a challenge for clinical use. More work is needed to understand the algorithm’s success and validity to determine its clinical viability.

Acute physiologic prediction of pediatric post-traumatic epilepsy

ObjectivePost-traumatic epilepsy (PTE) is a known complication of traumatic brain injury (TBI). Limited physiologic biomarkers have been investigated in relation to pediatric PTE. Our aim is to identify clinical, physiologic and neuroimaging biomarkers predictive of pediatric PTE arising during the acute care phase after injury. MethodsWe performed a retrospective analysis from a prospectively collected clinical database of pediatric patients who underwent multimodality neurologic monitoring that included continuous electroencephalography and intracranial pressure (ICP) monitoring. Biomarkers included hemodynamic vital signs, model-based indices of cerebrovascular pressure reactivity (CVPR) and autonomic function (AF), electroencephalographic abnormalities, and neuroimaging abnormalities on the initial CT scan on day of imaging. Our primary outcome, PTE, was classified as the presence of unprovoked seizures 2 months post-injury or the continued need for antiseizure medications at 12-month post-injury. We utilized univariate logistic regression to identify biomarkers associated with PTE. Results61 surviving patients were included in this study, among which 10 (16.4%) developed PTE. We identified that PTE was associated with increased ICP (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.02–1.52), increased pressure reactivity indices (92.53, 2.84->999.99), increased wavelet pressure reactivity indices (121.76, 2.84->999.99), increased CT Marshall scores (1.76, 1.13–2.74), decreased HRsd (0.54, 0.33–0.87) and the presence of epileptiform discharges (8.06, 1.85–35.17), and abnormal sleep spindles (4.88, 1.18–20.00). Whereas early post-traumatic seizures within the first 7 days post-injury were associated with PTE development (7.58, 1.81–39.68), this association was significant for such seizures occurring between 24 and 168 h post-injury (21.47, 4.18–110.38), and not for seizures occurring within 24 h post-injury. Among patients experiencing early post-traumatic seizures, increased time with seizures on surface electroencephalography was associated with PTE development (7.28, 2.05–73.14). We also identified that development of PTE was associated with worsened functional outcomes identified by increased Glasgow Outcome Scale – Extended Pediatric (GOSE-PEDs) scores (3.18, 1.68–8.01). ConclusionPediatric PTE development is associated with increased ICP, impaired CVPR, low heart rate variability, worsened neuroimaging findings, and electroencephalographic abnormalities identified during intensive care. Further studies are needed to investigate strategies to mitigate pediatric PTE development.

Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage: Relation to Neurointensive Care Targets

BackgroundThe primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome.MethodsIn this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO2 was defined as CDO2 < 3.8 mL O2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1–3) and vasospasm phase (day 4–14).ResultsOf 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions.ConclusionsSystemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.

Prolonged Automated Robotic TCD Monitoring in Acute Severe TBI: Study Design and Rationale.

Transcranial Doppler ultrasonography (TCD) is a portable, bedside, noninvasive diagnostic tool used for the real-time assessment of cerebral hemodynamics. Despite the evident utility of TCD and the ability of this technique to function as a stethoscope to the brain, its use has been limited to specialized centers because of the dearth of technical and clinical expertise required to acquire and interpret the cerebrovascular parameters. Additionally, the conventional pragmatic episodic TCD monitoring protocols lack dynamic real-time feedback to guide time-critical clinical interventions. Fortunately, with the recent advent of automated robotic TCD technology in conjunction with the automated software for TCD data processing, we now have the technology to automatically acquire TCD data and obtain clinically relevant informationin real-time. By obviating the need for highly trained clinical personnel, this technology shows great promise toward a future of widespread noninvasive monitoring to guide clinical care in patients with acute brain injury. Here, we describe a proposal for a prospective observational multicenter clinical trial to evaluate the safety and feasibility of prolonged automated robotic TCD monitoring in patients with severe acute traumatic brain injury (TBI). We will enroll patients with severe non-penetratingTBI with concomitant invasive multimodal monitoring including, intracranial pressure, brain tissue oxygenation, and brain temperature monitoring as part of standard of care in centers with varying degrees of TCD availability and experience. Additionally, we propose to evaluate the correlation of pertinent TCD-based cerebral autoregulation indicessuch as the critical closing pressure, and the pressure reactivity index withthe brain tissue oxygenationvaluesobtained invasively. The overarching goal of this study is to establish safety and feasibility of prolonged automated TCD monitoring for patients with TBI in the intensive care unit and identify clinically meaningful and pragmatic noninvasive targets for future interventions.

Vector Angle Analysis of Multimodal Neuromonitoring Data for Continuous Prediction of Delayed Cerebral Ischemia.

Dysfunctional cerebral autoregulation often precedes delayed cerebral ischemia (DCI). Currently, there are no data-driven techniques that leverage this information to predict DCI in real time. Our hypothesis is that information using continuous updated analyses of multimodal neuromonitoring and cerebral autoregulation can be deployed to predict DCI. Time series values of intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure (CPP), optimal CPP (CPPOpt), ΔCPP (CPP - CPPOpt), mean arterial pressure, and pressure reactivity index were combined and summarized as vectors. A validated temporal signal angle measurement was modified into a classification algorithm that incorporates hourly data. The time-varying temporal signal angle measurement (TTSAM) algorithm classifies DCI at varying time points by vectorizing and computing the angle between the test and reference time signals. The patient is classified as DCI+ if the error between the time-varying test vector and DCI+ reference vector is smaller than that between the time-varying test vector and DCI- reference vector. Finally, prediction at time point t is calculated as the majority voting over all the available signals. The leave-one-patient-out cross-validation technique was used to train and report the performance of the algorithms. The TTSAM and classifier performance was determined by balanced accuracy, F1 score, true positive, true negative, false positive, and false negative over time. One hundred thirty-one patients with aneurysmal subarachnoid hemorrhage who underwent multimodal neuromonitoring were identified from two centers (Columbia University: 52 [39.7%], Aachen University: 79 [60.3%]) and included in the analysis. Sixty-four (48.5%) patients had DCI, and DCI was diagnosed 7.2 ± 3.3days after hemorrhage. The TTSAM algorithm achieved a balanced accuracy of 67.3% and an F1 score of 0.68 at 165h (6.9days) from bleed day with a true positive of 0.83, false positive of 0.16, true negative of 0.51, and false negative of 0.49. A TTSAM algorithm using multimodal neuromonitoring and cerebral autoregulation calculations shows promise to classify DCI in real time.

Continuous Determination of the Optimal Bispectral Index Value Based on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A Retrospective Observational Cohort Study of a Novel Individualized Sedation Target.

BACKGROUND:We have sought to develop methodology for deriving optimal bispectral index (BIS) values (BISopt) for patients with moderate/severe traumatic brain injury, using continuous monitoring of cerebrovascular reactivity and bispectral electroencephalography.METHODS:Arterial blood pressure, intracranial pressure, and BIS (a bilateral measure that is associated with sedation state) were continuously recorded. The pressure reactivity index, optimal cerebral perfusion pressure (CPPopt), and BISopt were calculated. Using BIS values and the pressure reactivity index, a curve fitting method was applied to determine the minimum value for the pressure reactivity index thus giving the BISopt.RESULTS AND CONCLUSIONS:Identification of BISopt was possible in all of the patients, with both visual inspection of data and using our method of BISopt determination, demonstrating a similarity of median values of 44.62 (35.03–59.98) versus 48 (39.75–57.50) (p = 0.1949). Furthermore, our method outperformed common CPPopt curve fitting methods applied to BISopt with improved percent (%) yields on both the left side 52.1% (36.3–72.4%) versus 31.2% (23.0–48.9%) (p < 0.0001) and the right side 54.1% (35.95–75.9%) versus 33.5% (12.5–47.9%) (p < 0.0001). The BIS values and BISopt were compared with cerebral perfusion pressure, mean arterial pressure, and CPPopt. The results indicated that BISopt’s impact on pressure reactivity was distinct from CPPopt, cerebral perfusion pressure, or mean arterial pressure. Real-time BISopt can be derived from continuous physiologic monitoring of patients with moderate/severe traumatic brain injury. This BISopt value appears to be unassociated with arterial blood pressure or CPPopt, supporting its role as a novel physiologic metric for evaluating cerebral autoregulation. BISopt management to optimize cerebrovascular pressure reactivity should be the subject of future studies in moderate/severe traumatic brain injury.

Intracranial pressure dynamics and cerebral vasomotor reactivity in community-acquired bacterial meningitis during neurointensive care.

Community-acquired bacterial meningitis (CABM) is a severe condition associated with high mortality. In this study the first aim was to evaluate the incidence of intracranial pressure (ICP) insults and disturbances in cerebral vasomotor reactivity and the second aim was to evaluate the management and clinical outcome of CABM patients treated in the neurointensive care unit (NICU). CABM patients who were treated in the NICU of Uppsala University Hospital, Sweden, during 2008-2020 were included in the study. Data on demographics, admission variables, treatment, ICP dynamics, vasomotor reactivity, and short-term clinical outcome were evaluated in these patients. Of 97 CABM patients, 81 (84%) received ICP monitoring, of whom 22% had ICP > 20 mm Hg during 5% or more of the monitoring time on day 1, which decreased to 9% on day 3. For those patients with ICP monitoring, 46% required CSF drainage, but last-tier ICP treatment, including thiopental (4%) and decompressive craniectomy (1%), was rare. Cerebral vasomotor reactivity was disturbed, with a mean pressure reactivity index (PRx) above 0.2 in 45% of the patients on day 1, and remained high for the first 3 days. In total, 81 (84%) patients had a favorable outcome (Glasgow Coma Scale motor score [GCS M] 6) at discharge, 9 (9%) patients had an unfavorable outcome (GCS M < 6) at discharge, and 7 (7%) patients died in the NICU. Those with favorable outcome had significantly better cerebral vasomotor reactivity (lower PRx) than the two other outcome groups (p < 0.01). Intracranial hypertension was frequent following severe CABM and CSF drainage was often sufficient to control ICP. Cerebral vasomotor reactivity was commonly disturbed and associated with poor outcome. Clinical outcome was slightly better than in earlier studies.

Association of Arterial Metabolic Content with Cerebral Blood Flow Regulation and Cerebral Energy Metabolism-A Multimodality Analysis in Aneurysmal Subarachnoid Hemorrhage.

BackgroundIn this study, the association of the arterial content of oxygen, carbon dioxide, glucose, and lactate with cerebral pressure reactivity, energy metabolism and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH) was investigated.MethodsIn this retrospective study, 60 patients with aSAH, treated at the neurointensive care (NIC), Uppsala University Hospital, Sweden, between 2016 and 2021 with arterial blood gas (ABG), intracranial pressure, and cerebral microdialysis (MD) monitoring were included. The first 10 days were divided into an early phase (day 1 to 3) and a vasospasm phase (day 4 to 10).ResultsHigher arterial lactate was independently associated with higher/worse pressure reactivity index (PRx) in the early phase (β = 0.32, P = .02), whereas higher pO2 had the opposite association in the vasospasm phase (β = −0.30, P = .04). Arterial glucose and pCO2 were not associated with PRx. Higher arterial lactate (β = 0.29, P = .05) was independently associated with higher MD-glucose in the vasospasm phase, whereas higher pO2 had the opposite association in the vasospasm phase (β = −0.33, P = .03). Arterial glucose and pCO2 were not associated with MD-glucose. Higher pCO2 in the early phase, lower arterial glucose in both phases, and lower arterial lactate in the vasospasm phase were associated (P < .05) with better clinical outcome.ConclusionsArterial variables associated with more vasoconstriction (higher pO2 and lower arterial lactate) were associated with better cerebral pressure reactivity, but worse energy metabolism. In severe aSAH, when cerebral large-vessel vasospasm with exhausted distal vasodilation is common, more vasoconstriction could increase distal vasodilatory reserve and pressure reactivity, but also reduce cerebral blood flow and metabolic supply. The MD may be useful to monitor the net effects on cerebral metabolism in PRx-targeted NIC.

Dynamic Temporal Relationship Between Autonomic Function and Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury.

There has been little change in morbidity and mortality in traumatic brain injury (TBI) in the last 25 years. However, literature has emerged linking impaired cerebrovascular reactivity (a surrogate of cerebral autoregulation) with poor outcomes post-injury. Thus, cerebrovascular reactivity (derived through the pressure reactivity index; PRx) is emerging as an important continuous measure. Furthermore, recent literature indicates that autonomic dysfunction may drive impaired cerebrovascular reactivity in moderate/severe TBI. Thus, to improve our understanding of this association, we assessed the physiological relationship between PRx and the autonomic variables of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) using time-series statistical methodologies. These methodologies include vector autoregressive integrative moving average (VARIMA) impulse response function analysis, Granger causality, and hierarchical clustering. Granger causality testing displayed inconclusive results, where PRx and the autonomic variables had varying bidirectional relationships. Evaluating the temporal profile of the impulse response function plots demonstrated that the autonomic variables of BRS, ratio of low/high frequency of HRV and very low frequency HRV all had a strong relation to PRx, indicating that the sympathetic autonomic response may be more closely linked to cerebrovascular reactivity, then other variables. Finally, BRS was consistently associated with PRx, possibly demonstrating a deeper relationship to PRx than other autonomic measures. Taken together, cerebrovascular reactivity and autonomic response are interlinked, with a bidirectional impact between cerebrovascular reactivity and circulatory autonomics. However, this work is exploratory and preliminary, with further study required to extract and confirm any underlying relationships.

Optimal Cerebral Perfusion Pressure During Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

The recommendation of induced hypertension for delayed cerebral ischemia treatment after aneurysmal subarachnoid hemorrhage has been challenged recently and ideal pressure targets are missing. A new concept advocates an individual cerebral perfusion pressure where cerebral autoregulation functions best to ensure optimal global perfusion. We characterized optimal cerebral perfusion pressure at time of delayed cerebral ischemia and tested the conformity of induced hypertension with this target value. Retrospective analysis of prospectively collected data. University hospital neurocritical care unit. Thirty-nine aneurysmal subarachnoid hemorrhage patients with invasive neuromonitoring (20 with delayed cerebral ischemia, 19 without delayed cerebral ischemia). Induced hypertension greater than 180 mm Hg systolic blood pressure. Changepoint analysis was used to calculate significant changes in cerebral perfusion pressure, optimal cerebral perfusion pressure, and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure 48 hours before delayed cerebral ischemia diagnosis. Optimal cerebral perfusion pressure increased 30 hours before the onset of delayed cerebral ischemia from 82.8 ± 12.5 to 86.3 ± 11.4 mm Hg (p < 0.05). Three hours before delayed cerebral ischemia, a changepoint was also found in the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure (decrease from -0.2 ± 11.2 to -7.7 ± 7.6 mm Hg; p < 0.05) with a corresponding increase in pressure reactivity index (0.09 ± 0.33 to 0.19 ± 0.37; p < 0.05). Cerebral perfusion pressure at time of delayed cerebral ischemia was lower than in patients without delayed cerebral ischemia in a comparable time frame (cerebral perfusion pressure delayed cerebral ischemia 81.4 ± 8.3 mm Hg, no delayed cerebral ischemia 90.4 ± 10.5 mm Hg; p < 0.05). Inducing hypertension resulted in a cerebral perfusion pressure above optimal cerebral perfusion pressure (+12.4 ± 8.3 mm Hg; p < 0.0001). Treatment response (improvement of delayed cerebral ischemia: induced hypertension+ [n = 15] or progression of delayed cerebral ischemia: induced hypertension- [n = 5]) did not correlate to either absolute values of cerebral perfusion pressure or optimal cerebral perfusion pressure, nor the resulting difference (cerebral perfusion pressure [p = 0.69]; optimal cerebral perfusion pressure [p = 0.97]; and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure [p = 0.51]). At the time of delayed cerebral ischemia occurrence, there is a significant discrepancy between cerebral perfusion pressure and optimal cerebral perfusion pressure with worsening of autoregulation, implying inadequate but identifiable individual perfusion. Standardized induction of hypertension resulted in cerebral perfusion pressures that exceeded individual optimal cerebral perfusion pressure in delayed cerebral ischemia patients. The potential benefit of individual blood pressure management guided by autoregulation-based optimal cerebral perfusion pressure should be explored in future intervention studies.

Clinical Significance of Multiparameter Intracranial Pressure Monitoring in the Prognosis Prediction of Hypertensive Intracerebral Hemorrhage.

Objective: The present study aimed to investigate the clinical significance of multiparameter intracranial pressure (ICP) monitoring in the prediction of the prognosis of hypertensive intracerebral hemorrhage (HICH). Methods: A retrospective analysis was performed on the clinical data of 53 HICH patients. The patients underwent removal of intracranial hemorrhage and decompressive craniectomy after admission. A ventricular ICP monitoring probe was used to continuously and invasively monitor mean arterial pressure (MAP) and ICP after surgery. The NEUMATIC system was used to collect ICP data, including pressure reactivity index (PRx), ICP dose (DICP), amplitude and pressure regression (RAP), and cerebral perfusion pressure (CPP). The mean PRx, CPP, RAP, ICP, and DICP20 mmHg × h were calculated with 1 h as the time segment. According to the Glasgow outcome scale (GOS) scores after discharge, the patients were grouped into the poor prognosis group (GOS I–III) and the good prognosis group (GOS IV and V). The two groups were compared in terms of GOS scores in the treatment and prediction of prognosis of patients. Results: The good prognosis group showed significantly lower values of mean ICP, DICP20 mmHg × h, RAP, and PRx than the poor prognosis group, while CPP was significantly higher (p < 0.001). Conclusions: PRx, DICP, RAP, and CPP could reflect intracranial changes in patients and were significantly correlated with the prognosis of the patients. Mean ICP, PRx, DICP20 mmHg × h, and RAP were negatively correlated with prognosis, while CPP was positively correlated with prognosis.

Assessment of Optimal Arterial Pressure with Near-Infrared Spectroscopy in Traumatic Brain Injury Patients.

In patients with severe traumatic brain injury (TBI), simultaneous measurement of intracranial and arterial blood pressure (ICP and ABP, respectively) allows monitoring of cerebral perfusion pressure (CPP) and the assessment of cerebral autoregulation (CA). CPP, a difference between ICP and ABP, is the pressure gradient that drives oxygen delivery to cerebral tissue. CA is the ability of cerebral vasculature to maintain stable blood flow despite changes in CPP and thus, is an important homeostatic mechanism. Pressure reactivity index (PRx), a moving Pearson's correlation between slow waves in ICP and ABP, has been most frequently cited in literature over the past two decades as a tool for CA evaluation. However, in some clinical situations, ICP monitoring may be unavailable or contraindicated. In such cases, simultaneous mean arterial pressure (MAP) monitoring and near-infrared spectroscopy (NIRS) can be used for CA assessment by cerebral oximetry index (COx), allowing calculation of the optimal blood pressure (MAPOPT). The purpose of this study was to compare regional oxygen saturation (rSO2)-based CA (COx) with ICP/ABP-based CA (PRx) in TBI patients and to compare MAPOPT derived from both technologies. Three TBI patients were monitored at the bedside to measure CA using both PRx and COx. Patients were monitored daily for up to 3days from TBI. Averaged PRx and COx-, and PRx and COx-based MAPOPT were compared using Pearson's correlation. Bias analysis was performed between these same CA metrics. Correlation between averaged values of COx and PRx was R=0.35, p=0.15. Correlation between optimal MAP calculated for COx and PRx was R=0.49, p<0.038. Bland-Altman analysis showed moderate agreement with a bias of 0.16±0.23 for COx versus PRx and good agreement with a bias of 0.39±7.89 for optimal MAP determined by COx versus PRx. Non-invasive measurement of CA by NIRS (COx) is not correlated with invasive ICP/ABP-based CA (PRx). However, the determination of MAPOPT using COx is correlated with MAPOPT derived from PRx. Obtained results demonstrate that COx is not an acceptable substitute for PRx in TBI patients. However, in some TBI cases, NIRS may be useful in determining MAP determination.

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices, Chronological Age, and Biological Sex in Traumatic Brain Injury: A Scoping Review.

To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p < 0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p < 0.05) in the limited available literature. However, no literature exists comparing PAx or RAC with biological sex. Findings showed that aging was associated with impaired CVR. We observed a trend between female sex and worse PRx values, but the literature was limited and statistical significance was borderline. The identified studies were few in number, carried significant population heterogeneity, and utilized grand averaging of large epochs of physiology during statistical comparisons with age and biological sex. Because of the heterogeneous nature of TBI populations and limited focus on the effects of age and sex on outcomes in TBI, it is challenging to highlight the differences between the indices and patient age groups and sex. The largest study showing an association between PRx and age was done by Zeiler and colleagues, where 165 patients were studied noting that patients with a mean PRx value above zero had a mean age above 51.4 years versus a mean age of 41.4 years for those with a mean PRx value below zero (p = 0.0007). The largest study showing an association between PRx and sex was done by Czosnyka and colleagues, where 469 patients were studied noting that for patients <50 years of age, PRx was worse in females (0.11 ± 0.047) compared to males (0.044 ± 0.031), p < 0.05. The findings from these 10 studies provide preliminary data, but are insufficient to definitively characterize the impact of age and sex on CVR in moderate/severe TBI. Future work in the field should focus on the impact of age and sex on multi-modal cerebral physiological monitoring.

Relationship of Pressure Reactivity Index and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage (SAH) continue to have poor functional outcome due to the occurrence of delayed cerebral ischemia (DCI). Although vasospasm represents the primary therapeutic target for mitigating DCI, DCI occurs through multifocal etiologies that involve impaired cerebral autoregulation. Worse pressure reactivity index (PRx) values, which consists of a moving correlation coefficient between intracranial pressures and mean arterial pressures, have been shown to be associated with DCI in non-randomized clinical trials. We discuss two patients that presented with high-grade SAH and comatose exams. Patient one was a 34-year-old male diagnosed with SAH from a ruptured right middle cerebral artery aneurysm. He had intact PRx values (Mean: -0.07 during hospital days 9-19), while having severe, refractory vasospasm. At the conclusion of his hospitalization, he was functionally independent, had negligible DCI, and was successfully discharged home. Patient two was a 78-year-old female diagnosed with SAH from a ruptured anterior communicating artery aneurysm. She had an improving PRx ranging from -0.1 to 0.1 early in her hospitalization. However, upon developing severe vasospasm, her PRx increased to 0.6 (overall PRx from hospital days 4-16 was 0.3), and she suffered from extensive DCI in bilateral middle cerebral and anterior cerebral artery distributions that ultimately resulted in malignant cerebral edema and brain death. Cerebral autoregulation as measured by PRx may represent a viable target for neuroprognostication by evaluating DCI risk in patients with SAH who develop severe or refractory vasospasm. Further studies evaluating the role of cerebral autoregulation, PRx, and its pathophysiological role in DCI are warranted.